The Clinical Trials of Mesenchymal Stromal Cells Therapy

Abstract

Mesenchymal stromal cells (MSCs) are a heterogeneous population of adult stem cells, which are multipotent and possess the ability to differentiate/transdifferentiate into mesodermal and nonmesodermal cell lineages. MSCs display broad immunomodulatory properties since they are capable of secreting growth factors and chemotactic cytokines. Safety, accessibility, and isolation from patients without ethical concern make MSCs valuable sources for cell therapy approaches in autoimmune, inflammatory, and degenerative diseases. Many studies have been conducted on the application of MSCs as a new therapy, but it seems that a low percentage of them is related to clinical trials, especially completed clinical trials. Considering the importance of clinical trials to develop this type of therapy as a new treatment, the current paper is aimed at describing characteristics of MSCs and reviewing relevant clinical studies registered on the NIH database during 2016-2020 to discuss recent advances on MSC-based therapeutic approaches being used in different diseases.

Hematopoietic stem cell transplantation and cellular therapies for autoimmune diseases: overview and future considerations from the Autoimmune Diseases Working Party (ADWP) of the European Society for Blood and Marrow Transplantation (EBMT)

“…Their therapeutic application already demonstrated promising results in the context of spinal cord injury in rodents [ 111 ]. Other areas of investigation include the exploitation of the inherent biologic advantages of UCB stem cells with high proliferative potential and good damage repair capacity [ 112 ], and the biologic properties, therapeutic mechanisms and clinical efficacy of MSC or MSC-derived exosomes [ 113 , 114 ].…”

Optimization of Mesenchymal Stromal Cell (MSC) Manufacturing Processes for a Better Therapeutic Outcome

“…Given that in vitro expansion is always necessary for clinical escalation, we would select an MSC source that ensures large amounts of cells with high proliferation potential and capable of withstanding long periods in culture before acquiring genetic instability or a senescent profile ( 50 ). The most common sources of MSCs assessed in clinical trials have been umbilical cord, bone marrow, and adipose tissue ( 51 ), and although MSCs isolated from other sources have also being used, there is less experience with them ( Figure 1A ).…”

“…ADSCs show more genetic and morphologic stability in long-term cultures and faster proliferation than BM-MSC, even when harvested from the same donor. This is a clear advantage for large scale culture over BM-MSCs in which cultures beyond 20 days and passages beyond 6-7 are associated with senescence ( 51 ) ( Figure 1C ).…”

Isolation, Culture and Comprehensive Characterization of Biological Properties of Human Urine-Derived Stem Cells

“…The primary culture medium consisted of embryonic fibroblast medium (EFM) and keratinocyte serum free medium (KSFM, Cell Applications, San Diego, CA, USA) at the ratio 1:1, supplemented with 5% fetal bovine serum (FBS, PAN-Biotech, Aidenbach, Germany) and antibiotics Pen/Strept (Sigma-Aldrich, St. Louis, MO, USA). We also applied other supplements such as Renal Epithelial Growth Medium SingleQuots TM Kit (REGMTM, Lonza, Basel, Swiss) [6] and ROCK-Inhibitor (Sigma-Aldrich, St. Louis, MO, USA) with a final concentration of 10 µM. The primary medium was changed after 72 h with the fresh proliferation medium, and then, the changing of the medium was performed every 3 days.…”

“…In constantly stressed tissues and organs, mesenchymal stem cells (MSCs) ensure proper regeneration and maintenance of the physiological functions [5]. They are generally described as the cells with unique self-renewal abilities which can easily adhere to tissue culture dishes, express specific cell surface markers and can be differentiated into more than one specific cell lineage [6]. Tissue biopsy presents traditional way of their harvesting.…”